In recent years, the importance of improving patient compliance has been advocated, and for the purposes of allowing a patient whose ability of swallowing is weak, such as the elderly and an infant, to easily take medicine without water and of alleviating the burden of medicine administration care imposed on health care professionals, for example, by enabling a simplified suspension drug administration method, development and research of, for example, an orally disintegrating tablet which rapidly disintegrates in the oral cavity and when inputted into water, quickly disintegrates and disperses therein have been actively conducted.
As the methods for manufacturing the orally disintegrating tablet, there are three methods: as the first generation method, the so-called liquid drying method in which the orally disintegrating tablet is manufactured by pouring a drug and additive agent dispersed solution into a mold such as a blister pocket and drying is conducted; as the second generation method, the so-called wet molding method in which components constituted of drug and saccharides are formed into a wet lump, the wet lump is subjected to tableting molding at a low pressure, and thereafter, the resultant is dried; and as the third generation method, the so-called dry compression method in which the orally disintegrating tablet is manufactured by using an ordinary tableting apparatus by means of causing the functionality of a disintegrating tablet to develop through the selection of additives and elaborate formulation. Still now, many products are supplied by employing these tableting methods.
As the orally disintegrating tablets which have been so far marketed, there are many kinds of orally disintegrating tablets: such as the orally disintegrating tablet which has the very ordinary disintegrability and solubility; the orally disintegrating tablet which is manufactured by compounding drug particles prepared by directly coating drug itself with a bitter taste masking film; and the orally disintegrating tablet which is manufactured by compounding functional spherical fine particles, which are produced by preparing core fine particles prepared by layering drug to core particles and by coating the outer layers of the core fine particles with a release control film, an enteric film, or a bitter taste masking film.
Among the above-mentioned orally disintegrating tablets, in the case of the orally disintegrating tablet which is manufactured by producing the core fine particles prepared by layering the drug to the core particles, coating the outer layers of the core fine particles with the film having the functionality of the release control, the enteric coat, or the bitter taste masking, adding at least an excipient and a disintegrant to the coated particles obtained as mentioned above, and subjecting the resultant to compression molding, if the content of drug contained in one tablet is large, the tablet becomes large, thereby making it difficult to take the tablet. This is because the amount of the components, other than the drug, such as the core particles and the polymeric material forming the film inevitably becomes large.
Japanese Patent No. 3746167 discloses a granulated substance used for an orally disintegrating tablet, which is produced by layering an acid-unstable benzimidazole-based drug, for example, a mixture of lansoprazole and basic inorganic salt to core particles constituted of crystalline cellulose and lactose and further applying enteric coating thereto.
International Publication No. WO 2004/066991 discloses a method for manufacturing enteric sustained-release fine particles used for an orally disintegrating tablet, which includes the steps of: spraying a solution of hydroxypropyl methylcellulose, which contains tamsulosin hydrochloride, to core particles of crystalline cellulose or the like, thereby conducting layering; subsequently, applying sustained-release coating thereonto; and subsequently applying enteric coating thereonto.
Japanese Patent Application Laid-Open Publication No. 2012-240917 discloses fine particles used for manufacturing an orally disintegrating tablet which can be obtained by layering a coating liquid, prepared by adding drug in the form of acid addition salt and an inorganic or organic base to a water-soluble polymer solution, to spherical granules of crystalline cellulose; drying the resultant; and thereafter, applying a water-insoluble but water-permeable film thereonto. Although the water-insoluble water-permeable film coated onto the outermost layers of these fine particles suppresses diffusion and dissolution of the basic drug in the oral cavity, the water-insoluble water-permeable film is torn in the stomach or the upper part of the small intestine and the drug is released from the fine particles. Accordingly, in a case where these fine particles are used for manufacturing the orally disintegrating tablet, since the drug is not released in the oral cavity, the film applied onto the fine particles serves as a functional film which masks unpleasant taste of the drug.
Each of these particles obtained by layering the drug to the core particles of the crystalline cellulose or the like and further applying the functional film thereonto has a three-layer structure including at least a core particle in the center, a drug layer thereoutside, and the functional polymer layer further thereoutside, and thus, the particle diameter thereof inevitably becomes large.
In addition, a shape of each of the functional drug particles in the conventional technology, which have the core particles, depends on a shape of each of the core particles in the center and is thereby substantially spherical, and particle size distribution is comparatively narrow. Therefore, moldability into the tablet is inferior, and in order to manufacture a tablet having a hardness which can withstand the distribution in the market, it is required to increase a ratio of an excipient which allows easy molding.